Malaria remains a major health problem in the world. It has been estimated that at least 3,000 million people, nearly half of the world's population, are living in malaria endemic areas and between 300 and 500 million clinical cases and about 1.5 million deaths are reported annually [1]. The development of an effective vaccine would be an important achievement to help decrease the problem of this disease. The pre-erythrocytic vaccination approach has shown some efficacy in clinical trials with immunity to this stage of the malaria life cycle directed towards both the sporozoite and subsequent intrahepatic schizont [2]. The cellular immune response has previously been shown to be important in pre-erythrocytic immunity with CD8+ T cells and IFNγ production playing a major role in protection against liver stage malaria [3].
The thrombospondin-related adhesion protein (TRAP) is an antigen expressed on the sporozoites which has previously been shown to induce protective CD8+ T cell responses [4]. TRAP has been extensively tested in vaccine clinical trials as a fusion protein with a multiepitope string containing additional B-cell, CD8+ and CD4+ T cell epitopes from several malaria antigens, known as ME.TRAP [5, 6].
Vaccine vectors based on plasmid DNA or modified vaccinia virus Ankara (MVA) encoding the ME.TRAP antigen have been tested in the field (Moorthy et al. (2004) PLoS, Med 1(2): e33) and shown to induce high frequencies of effector T cells when used in a prime-boost regime.
Nevertheless, there remains a need for improved anti-malarial vaccines which are capable of preventing natural infection with Plasmodium falciparum in human subjects as well as inducing stronger T cell responses, particularly of the CD8+ type. In clinical trials of ME.TRAP as an insert in both DNA and poxvirus vectors, such as MVA and fowlpox, responses have been predominantly of the CD4+ type which are probably less protective than CD8+ T cell responses.
Adenoviral vectors of the human serotype 5 have previously been used in a P. yoelii mouse model of malaria and have shown outstanding immunogenicity and significant protection after just a single dose [7]. However, one major limitation preventing the use of this serotype in humans is the ubiquitous presence of AdH5, with frequent childhood infections resulting in seroconversion. To circumvent the problem of pre-existing immunity to AdH5, there has been increased interest in the use of adenoviral serotypes of simian origin that do not circulate in human populations, with a number of studies demonstrating the ability of these vectors to elicit CD8+ T-cell responses in both mice and nonhuman primate models of SARS [8] and HIV [9, 10].